Patent EP-2141163-A1 (EP)
Inventor: SCHULZE VOLKER
IPC: C07D417/14
Filed: 2008-07-02
Abstract: Substituted thiazolidinone compounds (I) are new. Substituted thiazolidinone compounds of formula (I) are new. R1 : optionally one or more times halo substituted 1-3C-alkyl or cyclopropyl; X : 1-3C-alkyl optionally one or more times substituted by cyano, methyl, ethyl, isopropyl, ethynyl, hydroxyl, aryl, furanyl or halo; Q : a substituted aromatic group of formula (a), where a single bone or a double bond is present between V1 and W1, W1 and U1, U1 and Y1, Y1 and Z, and Z and V1, where the bonds are = 2 double bond; V1, W1 : C or N; U1 : -CH 2-, -CH=, -CR2=, -N= or -NR3-; Y1 : -CH 2-, -CH=, -CR2=, -C=O-, -N= or -NR3-; Z : -CH 2-, -CH=, -CR2=, -O-, -N= or -NR3; R2 : 1-6C-(halo)alkyl, 1-6C-(halo)alkyloxy, (halo)-1-6C-alkoxy-1-6C-alkyl, -(CH 2) nC(O)NH 2, -(CH 2) nC(O)-R8, -(CH 2) nC(O)NR4R5, -(CH 2) nC(O) 2R6, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 3-10C-heterocycloalkyl, 6-10C-aryl, -(CH 2) m-6-10C-aryl, -(CH 2) nheteroaryl, -O(CH 2) p-6-10C-aryl, -O(CH 2) q-heteroaryl, -C(O) 2R6, -NR4R5, -C(O)NH 2, -C(O)-R8, -S(O)R7, -S(O) 2R7, -S(O) 2R8, -S(O) 2NR4R5, -C(O)H or -C(O)R7 (all optionally one or more times substituted by 1-6-(halo)alkyl, (halo)-1-6C-alkoxy-1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 3-10C-heterocycloalkyl, 6-10C-aryl, -(CH 2) m-6-10C-aryl, -(CH 2) nheteroaryl, -C(O)R7, -C(O) 2R6, -NR4R5, -C(O)NR4R5, -S(O)R7, -S(O) 2R7, -S(O) 2NR4R5, R8, R9, -(CH 2) nC(O)NR4R5 or -(CH 2) nC(O) 2R6), H, halo, CN or nitro; R3 : 1-6C-(halo)alkyl, (halo)-1-6C-alkoxy-1-6C-alkyl, -(CH 2) nC(O)NH 2, -(CH 2) nC(O)R8, -(CH 2) nC(O)NR4R5, -(CH 2) nC(O) 2R6, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 3-10C-heterocycloalkyl, 6-10C-aryl, -(CH 2) m-6-10C-aryl, -(CH 2) nheteroaryl, -C(O) 2R6, -C(O)NH 2, -C(O)R8,, -C(O)NR4R5, -S(O)R7, -S(O) 2R7, -S(O) 2R8 or -S(O) 2NR4R5 (all optionally one or more times substituted by 1-6C-(halo)alkyl, (halo)-1-6C-alkoxy-1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 3-10C-heterocycloalkyl, 6-10C-aryl, -(CH 2) m-6-10C-aryl, -(CH 2) nheteroaryl, -C(O)R7, -C(O) 2R6, -NR4R5, -C(O)NR4R5, -S(O)R7, -S(O) 2R7, -S(O) 2NR4R5, R8, R9, -(CH 2) nC(O)NR4R5 or -(CH 2) nC(O) 2R6), or CN, -C(O)H or -C(O)R7; R4, R5 : H, 1-6C-(halo)alkyl, (halo)-1-6C-alkoxy-1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 6-10C-aryl, heteroaryl, -(CH 2) m-6-10C-aryl, or -(CH 2) nheteroaryl; R6 : H, 1-6C-(halo)alkyl, (halo)-1-6C-alkoxy-1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 6-10C-aryl, heteroaryl, -(CH 2) m-6-10C-aryl, or -(CH 2) nheteroaryl; R7 : 1-6C-(halo)alkyl, (halo)-1-6C-alkoxy-1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 6-10C-aryl, heteroaryl, -(CH 2) m-6-10C-aryl, or -(CH 2) nheteroaryl; R8 : 3-10C-heterocycloalkyl (optionally one or more times substituted by 1-6C-(halo)alkyl, (halo)1-6C-alkoxy-1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 3-10C-heterocycloalkyl, 6-10C-aryl, -(CH 2) m-6-10C-aryl, -(CH 2) nheteroaryl, -C(O)R7, -C(O) 2R6, -NR4R5, -C(O)NR4R5, -S(O)R7, -S(O) 2R7, -S(O) 2NR4R5, -(CH 2) nC(O)NR4R5 or -(CH 2) nC(O) 2R6); R9 : 3-10C-cycloalkyl (optionally one or more times substituted by 1-6C-(halo)alkyl, (halo)-1-6C-alkoxy-1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 3-10C-cycloalkyl, 3-10C-heterocycloalkyl, 6-10C-aryl, -(CH 2) m-6-10C-aryl, -(CH 2) nheteroaryl, -C(O)R7, -C(O) 2R6, -NR4R5, -C(O)NR4R5 -S(O)R7, -S(O) 2R7, -S(O) 2NR4R5, -(CH 2) nC(O)NR4R5 or -(CH 2) nC(O) 2R6); and n, m, p, q : 1-4. Independent claims are included for: (1) the preparations of (I); and (2) isothiazolidin-3-one compounds of formula (II) and (VII). P1 : 1-6C-alkyl. [Image] [Image] [Image] ACTIVITY : Cytostatic; Immunosuppressive; Antipsoriatic; Endocrine-Gen.; Neuroprotective; Antiinflammatory; Cardiovascular-Gen.; Vasotropic; Antiarteriosclerotic; Antiparasitic; Protozoacide; Antimalarial; Fungicide; Nephrotropic; Anticonvulsant; Nootropic; Antiparkinsonian; Virucide; Hepatotropic; Anti-HIV. MECHANISM OF ACTION : Polo-like kinase inhibitor. The ability of (I) to inhibit polo-like kinase was tested in insect cell (Hi5). The results showed that (Z,E/Z)-2-cyan-2-[3-ethyl-5-[[[1-(1-methyl-4-piperidinyl)-1H-indol-6-yl]amino]methylen]-4-oxo-2-thiazolidinyliden]-N-(2-hydroxy-1,1-dimethylethyl)acetamide exhibited an IC 5 0 value of 1 M.